The broad objective of this project is to identify the intercellular signals which influence cell fate specification in the early embryo, particularly the cardiac fate. Identification of these signals may help to identify the causes of defects in heart formation and differentiation. Specifically, a screen for growth factor molecules which act alone or in combination with BMP-2 in the chick gastrula to specify primitive streak explants as cardiac myoblasts will be undertaken. The function of these molecules will be tested by addition of cells expressing these factors to cultures, by specific inhibition with antisense oligonucleotides and by general inhibition with dominant-negative receptors for BMP family members. Identification of tissues which inhibit heart formation in primitive streak cells will also be attempted. Candidate signaling molecules known to be secreted from neural plate and notochord will be tested for inhibition of cardiac myocyte differentiation in an explant assay.